1-Thiadiazoly-6-carbamoyloxytetrahydropyrimidinones

ABSTRACT

Disclosed are new compounds of the formula ##EQU1## wherein R 1  is selected from the group consisting of alkyl, alkenyl, haloalkyl, alkoxy, alkylthio, alkylsulfonyl and alkylsulfinyl; R 2  is selected from the group consisting of alkyl, alkenyl, haloalkyl and ##EQU2## wherein R 3  and R 4  are each selected from the group consisting of hydrogen and alkyl; R 5  is selected from the group consisting of hydrogen and alkyl; and R 6  is selected from the group consisting of alkyl, cycloalkyl and ##SPC1## 
     Wherein X is selected from the group consisting of alkyl, halogen, haloalkyl and alkoxy, and n is an integer from 0 to 3. The subject compounds are useful as herbicides.

This invention relates to new compositions of matter and morespecifically relates to new chemical compounds of the formula ##EQU3##wherein R¹ is selected from the group consisting of alkyl, alkenyl,haloalkyl, alkoxy, alkylthio, alkylsulfonyl and alkylsulfinyl; R² isselected from the group consisting of alkyl, alkenyl, haloalkyl and##EQU4## wherein R³ and R⁴ are each selected from the group consistingof hydrogen and alkyl; R⁵ is selected from the group consisting ofhydrogen and alkyl; and R⁶ is selected from the group consisting ofalkyl, cycloalkyl and ##SPC2##

Wherein X is selected from the group consisting of alkyl, halogen,haloalkyl and alkoxy, and n is an integer from 0 to 3.

In a preferred embodiment of the present invention R¹ is selected fromthe group consisting of lower alkyl, lower alkenyl, lower chloroalkyl,lower bromoalkyl, trifluoromethyl, lower alkoxy, lower alkylthio, loweralkylsulfonyl and lower alkylsulfinyl; R² is selected from the groupconsisting of lower alkyl, lower alkenyl, lower chloroalkyl, lowerbromoalkyl and ##EQU5## wherein R³ and R⁴ are each selected from thegroup consisting of hydrogen and lower alkyl; R⁵ is selected from thegroup consisting of hydrogen and lower alkyl; and R⁶ is selected fromthe group consisting of lower alkyl, cycloalkyl of from 3 to 7 atoms and##SPC3##

Wherein X is selected from the group consisting of lower alkyl, loweralkoxy, halogen and lower haloalkyl.

The term lower as used herein designates a straight or branched carbonchain of up to six carbon atoms.

The compounds of the present invention are unexpectedly useful asherbicides.

The compounds of this invention wherein R⁵ is hydrogen can be readilyprepared by reacting a compound of the formula ##EQU6## wherein R¹ andR² are as heretofore described, with an isocyanate of the formula

    R.sup.6 -- N = C = O                                       (III)

wherein R⁶ is as heretofore described. This reaction can be effected bycombining the compound of formula II with an about equimolar or slightexcess molar amount of the isocyanate of formula III at room temperatureand in the presence of a catalytic amount of triethylamine. An inertorganic solvent can be used if desirable. The reaction mixture can bestirred at room temperature, or at elevated temperatures if the reactionproceeds slowly, and can then be let stand for a period of up to about 3hours to ensure completion of the reaction. After this time excessisocyanate if used can be removed by vacuum stripping to yield thedesired product which can be used as such or can be further purified byconventional means such as washing, recrystallizing and the like.

The compounds of the present invention wherein R⁵ is alkyl can beprepared by reacting a compound of formula II with a carbamoyl chlorideof the formula ##EQU7## wherein R⁵ is alkyl and R⁶ is as heretoforedescribed. This reaction can be effected by combining about equimolaramounts of the compounds of formulae II and IV in an inert organicsolvent such as toluene or xylene in the presence of an acid acceptorsuch as a tertiary amine or alkali metal carbonate or hydroxide. Thereaction mixture can then be heated at reflux for a period of from aboutone-half to about 4 hours. After this time the reaction mixture can befiltered to remove acid acceptor salt and can then be stripped ofsolvent under vacuum to yield the desired product as the residue. Thisproduct can be used as such or can be further purified by washing,recrystallizing and the like.

The compounds of formula II can be prepared by heating a compound of theformula ##EQU8## wherein R¹ and R² are as heretofore described and R⁷and R⁸ are methyl or ethyl, in a dilute, aqueous, acidic reaction mediumfor a period of about 10 to about 60 minutes. Temperatures of from about70°C to the reflux temperature of the reaction mixture can be utilized.The reaction medium can comprise a dilute aqueous inorganic acid such ashydrochloric acid at a concentration of from about 0.5 to about 5percent. Upon completion of the reaction the desired product can berecovered as a precipitate by cooling the reaction mixture. This productcan be used as such or can be further purified by conventional meanssuch as recrystallization and the like.

The compounds of formula V can be prepared by reacting a molar amount ofan isocyanate dimer of the formula ##EQU9## wherein R¹ is as heretoforedescribed, with about two molar amounts of an acetal of the formula##EQU10## wherein R², R⁷ and R⁸ are as heretofore described. Thisreaction can be effected by heating a mixture of the isocyanate dimerand the acetal in an inert organic reaction medium such as benzene atthe reflux temperature of the reaction mixture. Heating at reflux can becontinued for a period of from about 2 to about 30 minutes to ensurecompletion of the reaction. After this time the desired product can berecovered upon evaporation of the reaction medium and can be used assuch or can be further purified by standard techniques in the art.

The isocyanate dimer of formula VI can be prepared by reacting athiadiazole of the formula ##EQU11## wherein R¹ is as heretoforedescribed, with phosgene. This reaction can be effected by adding aslurry or solution of the thiadiazole, in a suitable organic solventsuch as ethyl acetate, to a saturated solution of phosgene in an organicsolvent such as ethyl acetate. The resulting mixture can be stirred atambient temperatures for a period of from about 4 to 24 hours. Thereaction mixture can then be purged with nitrogen gas to removeunreacted phosgene. The desired product can then be recovered byfiltration if formed as a precipitate or upon evaporation of the organicsolvent used if soluble therein. This product can be used as such or canbe further purified if desired.

Exemplary thiadiazoles of formula V useful for preparing the compoundsof the present invention are 5-methyl-2-amino-1,3,4-thiadiazole,5-ethyl- 2-amino-1,3,4-thiadiazole, 5-propyl-2-amino-1,3,4-thiadiazole,5-allyl-2-amino-1,3,4-thiadio-zole,5-pent-3-enyl-2-amino-1,3,4-thiadiazole,5-chloromethyl-2-amino-1,3,4-thiadiazole,5-β-chloroethyl-2-amino-1,3,4-thiadiazole,5-γ-chloropropyl-2-amino-1,3,4-thiadiazole,5-trichloromethyl-2-amino-1,3,4-thiadiazole,5-methoxy-2-amino-1,3,4-thiadiazole, 5-ethoxy-2-amino-1,3,4-thiadiazole,5-propoxy-2-amino-1,3,4-thiadioazole,5-butyloxy-2-amino-1,3,4-thiadiazole,5-hexyloxy-2-amino-1,3,4-thiadiazole,5-methylthio-2-amino-1,3,4-thiadiazole,5-ethylthio-2-amino-1,3,4-thiadiazole,5-propylthio-2-amino-1,3,4-thiadiazole,5-butylthio-2-amino-1,3,4-thiadiazole,5-methylsulfonyl-2-amino-1,3,4-thiadiazole,5-ethylsulfonyl-2-amino-1,3,4-thiadiazole,5-butylsulfonyl-2-amino-1,3,4-thiadiazole,5-methylsulfinyl-2-amino-1,3,4-thiadiazole,5-ethylsulfinyl-2-amino-1,3,4-thiadiazole, 5-propylsulfinyl-2-amino-1,3,4-thiadiazole, 5-t-butyl-2-amino-1,3,4-thiadiazole,5-trifluoromethyl-2-amino-1,3,4thiadiazole and the like.

The acetal of formula VII when not readily available can be prepared byreacting an amine of the formula ##EQU12## wherein R² is as heretoforedescribed with dimethyl or diethyl acetal of β-bromopropionaldehyde.This reaction can be effected by combining from about 1 to about 2 molaramounts of the amine of formula IX with one molar amount of the acetalof β-bromopropionaldehyde in about equimolar proportions in an inertorganic reaction medium such as methanol. The reaction mixture can thenbe heated at reflux for a period of from about 4 to about 8 hours. Afterthis time the reaction mixture can be cooled to room temperature and analkali metal hydroxide or carbonate can be added in an amount sufficientto neutralize the reaction mixture. Stirring can be continued at roomtemperature for a period of up to about 24 hours to ensure completion ofthe reaction. After this time the reaction mixture can be filtered andthe filtrate distilled under reduced pressure to yield the desiredproduct.

Exemplary compounds of formula IX are methylamine, ethylamine,propylamine, isopropylamine, n-butylamine, t-butylamine, pentylamine,hexylamine, allylamine, propargylamine, 2-butenylamine, 3-butenylamine,3pentenylamine, 4-pentenylamine, 5-hexenylamine,1-methyl-2-propynylamine, 1,1-dimethyl-2-propynylamine,1-ethyl-2-propynylamine, 1,1-diethyl-2-propynylamine,1-propyl-2-propynylamine, 1,1-dipropyl-2-propynylamine,1-chloroallylamine, 1-bromoallylamine, 4-chloro-2-butenylamine,6-chloro-4-hexenylamine and the like.

Exemplary isocyanates of formula III useful in preparing the compoundsof the present invention are methyl isocyanate, ethyl isocyanate, propylisocyanate, butyl isocyanate, hexyl isocyanate, cyclopropyl isocyanate,cyclobutyl isocyanate, cyclopentyl isocyanate, cyclohexyl isocyanate,cycloheptyl isocyanate, phenyl isocyanate, 2-methylphenyl isocyanate,4-ethylphenyl isocyanate, 4-butylphenyl isocyanate, 4-hexylphenylisocyanate, 2-chlorophenyl isocyanate, 2,4-dichlorophenyl isocyanate,2-methyl-4-chlorophenyl isocyanate, 3-bromophenyl isocyanate,4-iodophenyl isocyanate, 4-fluorophenyl isocyanate, 2-methoxyphenylisocyanate, 3-ethoxyphenyl isocyanate, 4hexyloxylphenyl isocyanate,4-trifluoromethylphenyl isocyanate, 4-chloromethylphenyl isocyanate,4-β-bromoethylphenyl isocyanate, 3-ω-chlorohexylphenyl isocyanate andthe like.

Exemplary useful carbamoyl chlorides of formula IV areN,N-dimethylcarbamoyl chloride, N,N-diethylcarbamoyl chloride,N,N-dipropylcarbamoyl chloride, N,N-dibutylcarbamoyl chloride,N,N-dihexylcarbamoyl chloride, N-methyl-N-cyclopropylcarbamoyl chloride,N-methyl-N-cyclohexylcarbamoyl chloride, N-methyl-N-cycloheptylcarbamoylchloride, N-ethyl-N-cycloheptylcarbamoyl chloride,N-methyl-N-phenylcarbamoyl chloride, N-ethyl-N-phenylcarbamoyl chloride,N-methyl-N-(2-methylphenyl)carbamoyl chloride,N-methyl-N-(2-ethylpheyl)-carbamoyl chloride,N-methyl-N-(2-propylphenyl)carbamoyl chloride,N-methyl-N-(4-chlorophenyl)carbamoyl chloride,N-methyl-N-(4-bromophenyl)carbamoyl chloride,N-methyl-N-(2-methoxyphenyl)carbamoyl chloride,N-methyl-N-(4-trifluoromethylphenyl)carbamoyl chloride and the like.

The manner in which the compounds of the present invention can beprepared is more specifically illustrated in the following examples.

EXAMPLE 1 Preparation of 5-Methyl-1,3,4-thiadiazol-2-yl Isocyanate Dimer

A saturated solution of phosgene in ethyl acetate (100 ml) is chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-methyl-2-amino-1,3,4-thiadiazole (40 grams) in ethyl acetate(300 ml) is added to the reaction vessel and the resulting mixture isstirred for a period of about 16 hours, resulting in the formation of aprecipitate. The reaction mixture is then purged with nitrogen gas toremove unreacted phosgene. The purged mixture is then filtered torecover the precipitate. The precipitate is then recrystallized to yieldthe desired product 5-methyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

EXAMPLE 2 Preparation of the Dimethyl Acetal of3-Methylaminopropionaldehyde

Methylamine (1.0 mole), the dimethyl acetal of 3-bromopropionaldehyde(0.5 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux, with stirring, fora period of about 4 hours. After this time the reaction mixture iscooled to room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 8hours. The reaction mixture is then filtered and the filtrate isdistilled under reduced pressure to yield the desired product thedimethyl acetal of 3-methylaminopropionaldehyde.

EXAMPLE 3 Preparation of the Dimethyl Acetal of3-[1-Methyl-3-(5-methyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methyl-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05mole), the dimethyl acetal of 3-methylaminopropionaldehyde (0.1 mole)and benzene (60 ml) are charged into a glass reactions vessel equippedwith a mechanical stirrer and reflux condenser. The reaction mixture isheated at reflux for a period of about 15 minutes. After this time themixture is stripped of benzene under reduced pressure to yield a solidproduct as the residue. The residue is then recrystallized to yield thedesired product the dimethyl acetal of3-[1-methyl-3-(5-methyl-1,3,4-thiadiazol-2-yl)-ureido]propionaldehyde.

EXAMPLE 4 Preparation ofTetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-methyl-3-(5-methyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde (15grams), water (400 ml) and hydrochloric acid (4 ml) are charged into aglass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reactiom mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2-(1H)-pyrimidinone.

EXAMPLE 5 Preparation ofTetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N-methylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and methyl isocyanate (3.5 ml; 0.06 mole) are charged into aglass reaction vessel equipped with a mechanical stirrer. The mixture isstirred and triethylamine (1 drop) is added thereto. After the additionis completed the reaction mixture is allowed to stand for a period ofabout 1 hour. The mixture is then washed with hexane and is dried toyield the desired producttetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N-methylcarbamoyloxy)-2(1H)-pyrimidinone.

EXAMPLE 6 Preparation of 5-Methoxy-1,3,4-thiadiazol-2-yl IsocyanateDimer

A saturated solution of phosgene in ethyl acetate (100 ml) is chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-methoxy-2-amino-1,3,4-thiadiazole (40 grams) in ethylacetate (300 ml) is added to the reaction vessel and the resultingmixture is stirred for a period of about 16 hours, resulting in theformation of a precipitate. The reaction mixture is then purged withnitrogen gas to remove unreacted phosgene. The purged mixture is thenfiltered to recover the precipitate. The precipitate is thenrecrystallized to yield the desired product5-methoxy-1,3,4-thiadizol-2-yl isocyanate dimer.

EXAMPLE 7 Preparation of the Dimethyl Acetal of3-Ethylaminopropionaldehyde

Ethylamine (2.0 mole), the dimethyl acetal of 3-bromopropionaldehyde(1.0 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux,, with stirring, fora period of about 5 hours. After this time the reaction mixture iscooled to room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 12hours. The reaction mixture is then filtered and the filtrate isdistilled under reduced pressure to yield the desired product thedimethyl acetal of 3-ethylaminopropionaldehyde.

EXAMPLE 8 Preparation of the Dimethyl Acetal of3-[1-(Ethyl-3-(5-methoxy-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05mole), the dimethyl acetal of 3-ethylaminopropionaldehyde (0.1 mole) andbenzene (60 ml) are charged into a glass reaction vessel equipped with amechanical stirrer and reflux condenser. The reaction mixture is heatedat reflux for a period of about 15 minutes. After this time the mixtureis stripped of benzene under reduced pressure to yield a solid productas the residue, The residue is then recrystallized to yield the desiredproduct the dimethyl acetal of3-[1-ethyl-3-(5-methoxy-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 9 Preparation ofTetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-ethyl-3-(5-methoxy-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde (15grams), water (400 ml) and hydrochloric acid (4 ml) are charged into aglass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 10 Preparation ofTetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-(N-cyclopropylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and cyclopropyl isocyanate (3.5 ml; 0.07 mole) are chargedinto a glass reaction vessel equipped with a mechanical stirrer. Themixture is stirred and triethylamine (1 drop) is added thereto. Afterthe addition is completed the reaction mixture is allowed to stand for aperiod of about 1 hour. The mixture is then washed with hexane and isdried to yield the desired producttetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-(N-cyclopropylcarbamoyloxy)-2(1H)-pyrimidinone.

EXAMPLE 11 Preparation of 5-Methylthio-1,3,4-thiadiazol-2-yl IsocyanateDimer

A saturated solution of phosgene in ethyl acetate (100 ml) is chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-methylthio-2-amino-1,3,4-thiadiazole (45 grams) in ethylacetate (300 ml) is added to the reaction vessel and the resultingmixture is stirred for a period of about 16 hours, resulting in theformation of a precipitate. The reaction mixture is then purged withnitrogen gas to remove unreacted phosgene. The purged mixture is thenfiltered to recover the precipitate. The precipitate is thenrecrystallized to yield the desired product5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer.

EXAMPLE 12 Preparation of the Dimethyl Acetal of3-Propylaminopropionaldehyde

Propylamine (2.0 mole), the dimethyl acetal of 3-bromopropionaldehyde(1.0 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux, with stirring, fora period of about 3 hours. After this time the reaction mixture iscooled to room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 6hours. The reaction mixture is then filtered and the filtrate isdistilled under reduced pressure to yield the desired product thedimethyl acetal of 3-propylaminopropionaldehyde.

EXAMPLE 13 Preparation of the Dimethyl Acetal of3-[1-Propyl-3-(5-methylthio-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05mole), the dimethyl acetal of 3-propylaminopropionaldehyde (0.1 mole)and benzene (60 ml) are charged into a glass reaction vessel equippedwith a mechanical stirrer and reflux condenser. The reaction mixture isheated at reflux for a period of about 15 minutes. After this time themixture is stripped of benzene under pressure to yield a solid productas the residue. The residue is then recrystallized to yield the desiredproduct the dimethyl acetal of3-[1-propyl-3-(5-methylthio-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 14 Preparation ofTetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-propyl-3-(5-methylthio-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 15 Preparation ofTetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-(N-cyclohexylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and cyclohexyl isocyanate (3.5 ml); 0.06 mole) are chargedinto a glass reaction vessel equipped with a mechanical stirrer. Themixture is stirred and triethylamine (1 drop) is added thereto. Afterthe addition is completed the reaction mixture is allowed to stand for aperiod of about 1 hour. The mixture is then washed with hexane and isdried to yield the desired producttetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-(N-cyclohexylcarbamoyloxy)-2(1H)-pyrimidinone.

EXAMPLE 16 Preparation of 5-Methylsulfonyl-1,3,4-thiadiazol-2-ylIsocyanate Dimer

A saturated solution of phosgene in ethyl acetate (100 ml) is chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-methylsulfonyl-2-amino-1,3,4-thiadiazole (50 grams) in ethylacetate (300 ml) is added to the reaction vessel and the resultingmixture is stirred for a period of about 16 hours, resulting in theformation of a precipitate. The reaction mixture is then purged withnitrogen gas to remove unreacted phosgene. The purged mixture is thenfiltered to recover the precipitate. The precipitate is thenrecrystallized to yield the desired product5-methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

EXAMPLE 17 Preparation of the Dimethyl Acetal of3-Allylaminopropionaldehyde

Allylamine (1.0 mole), the dimethyl acetal of 3-bromopropionaldehyde(0.5 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux, with stirring, fora period of about 8 hours. After this time the reaction mixture iscooled to room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 14hours. The reaction mixture is then filtered and the filtrate isdistilled under reduced pressure to yield the desired product thedimethyl acetal of 3-allylaminopropionaldehyde.

EXAMPLE 18 Preparation of the Dimethyl Acetal of3-[1-Allyl-3-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer(0.05 mole), the dimethyl acetal of 3-allylaminopropionaldehyde (0.1mole) and benzene (60 ml) are charged into a glass reaction vesselequipped with a mechanical stirrer and reflux condenser. The reactionmixture is heated at reflux for a period of about 15 minutes. After thistime the mixture is stripped of benzeneunder reduced pressure to yield asolid product as the residue. The residue is then recrystallized toyield the desired product the dimethyl acetal of3-[1-allyl-3-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 19 Preparation ofTetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-methyl-3-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-hydroxy-2(1H)-pyrimidione.

EXAMPLE 20 Preparation ofTetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-[N-(3-chlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and 3-chlorophenyl isocyanate (3.5 ml; 0.06 mole) arecharged into a glass reaction vessel equipped with a mechanical stirrer.The mixture is stirred and triethylamine (1 drop) is added thereto.After the addition is completed the reaction mixture is allowed to standfor a period of about 1 hour. The mixture is then washed with hexane andis dried to yield the desired producttetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-[N-(3-chlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 21 Preparation of 5-Methylsulfinyl-1,3,4-thiadiazol-2-ylIsocyanate Dimer

A saturated solution of phosgene in ethyl acetate (100 ml) is chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-methylsulfinyl-2-amino-1,3,4-thiadiazole (50 grams) in ethylacetate (300 ml) is added to the reaction vessel and the resultingmixture is stirred for a period of about 16 hours, resulting in theformation of a precipitate. The reaction mixture is then purged withnitrogen gas to remove unreacted phosgene. The purged mixture is thenfiltered to recover the precipitate. The precipitate is thenrecrystallized to yield the desired product5-methylsulfinyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

EXAMPLE 22 Preparation of the Dimethyl Acetal of3-Propargylaminopropionaldehyde

Propargylamine (2.0 mole), the dimethyl acetal of 3-bromopropionaldehyde(1.0 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux, with stirring, fora period of about 6 hours. After this time the reaction mixture iscooled to room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 18hours. The reaction mixture is then filtered and the filtrate isdistilled under reduced pressure to yield the desired product thedimethyl acetal of 3-propargylaminopropionaldehyde.

EXAMPLE 23 Preparation of the Dimethyl Acetal of3-[1-Propargyl-3-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methylsulfinyl-1,3,4-thiadiazul-2-yl isocyanate dimer(0.05 mole), the dimethyl acetal of 3-propargylaminopropionaldehyde (0.1mole) and benzene (60 ml) are charged into a glass reaction vesselequipped with a mechanical stirrer and reflux condenser. The reactionmixture is heated at reflux for a period of about 15 minutes. After thistime the mixture is stripped of benzene under reduced pressure to yielda solid product as the residue. The residue is then recrystallized toyield the desired product the dimethyl acetal of3-[1-propargyl-3-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 24 Preparation ofTetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-propargyl-3-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 25 Preparation ofTetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-[N-(2-methyl-4-bromophenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and 2-methyl-4-bromophenyl isocyanate (3.5 ml; 0.06 mole)are charged into a glass reaction vessel equipped with a mechanicalstirrer. The mixture is stirred and triethylamine (1 drop) is addedthereo. After the addition is completed the reaction mixture is allowedto stand for a period of about 1 hour. The mixture is then washed withhexane and is dried to yield the desired producttetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-[N-(2-methyl-4-bromophenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 26 Preparation of 5-Trifluoromethyl-1,3,4-thiadiazol-2-ylIsocyanate Dimer

A saturated solution of phosgene in ethyl acetate (100 ml) was chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-trifluoromethyl-2-amino-1,3,4-thiadiazole (45 grams) inethyl acetate (300 ml) was added to the reaction vessel and theresulting mixture was stirred for a period of about 16 hours resultingin the formation of a precipitate. The reaction mixture was then purgedwith nitrogen gas to remove unreacted phosgene. The purged mixture wasfiltered to recover 48 grams of a white solid. This solid wasrecrystallized from dimethyl formamide to yield the desired product5-trifluoromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer.

EXAMPLE 27 Preparation of the Dimethyl Acetal of2-[1-Methyl-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-trifluoromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer(9.5 grams), the dimethyl acetal of 3-methylaminopropionaldehyde (5.8grams) and benzene (60 ml) are charged into a glass reaction vesselequipped with a mechanical stirrer and reflux condenser. The reactionmixture is heated at reflux for a period of about 15 minutes. After thistime the mixture is stripped of benzene under reduced pressure to yielda solid product as the residue. This product is recrystallized to yieldthe desired product the dimethyl acetal of3-[1-methyl-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 28 Preparation ofTetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-methyl-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled resulting in the formation of aprecipitate. The precipitate is recovered by filtration, is dried and isrecrystallized to yield the desired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 29 Preparation ofTetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N,N-dimethylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N,N-dimethylcarbamoyl chloride (0.06 mole), pyridine (0.06mole) and toluene (150 ml) are charged into a glass reaction vesselequipped with a mechanical stirrer, thermometer and reflux condenser.The reaction mixture is heated at reflux with stirring for a period ofabout 3 hours. After this time the reaction mixture is cooled to roomtemperature and is filtered to remove pyridine hydrochloride. Thefiltrate is then washed with water, dried over anhydrous magnesiumsulfate and stripped of solvent leaving a residue. The residue isrecrystallized to yield the desired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N,N-dimethylcarbamoyloxy-2(1H)-pyrimidinone.

EXAMPLE 30 Preparation of 5-t-Butyl-1,3,4-thiadiazol-2-yl IsocyanateDimer

A saturated solution of phosgene in ethyl acetate (100 ml) was chargedinto a glass reaction vessel equipped with a mechanical stirrer. Aslurry of 5-t-butyl-2-amino-1,3,4-thiadiazole (10 grams) in ethylacetate (300 ml) was added to the reaction vessel and the resultingmixture was stirred for a period of about 16 hours resulting in theformation of a precipitate. The reaction mixture was then purged withnitrogen gas to remove unreacted phosgene. The purged mixture was thenfiltered to recover the desired product 5-t-butyl-1,3,4-thiadiazol-2-ylisocyanate dimer as a solid having a melting point of 261° to 263°C.

EXAMPLE 31 Preparation of the Dimethyl Acetal of3-[1-Methyl-3-(5-t-butyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-t-butyl-1,3,4-thiadiazol-2-yl isocyanate dimer (6 grams),the dimethyl acetal of 3-methylaminopropionaldehyde (4.0 grams) andbenzene (50 ml) are charged into a glass reaction flask equipped with amechanical stirrer and reflux condenser. The reaction mixture is heatedat reflux, with stirring, for a period of about 5 minutes. After thistime the reaction mixture is stripped of benzene to yield a residue. Theresidue is then recrystallized to yield the desired product the dimethylacetal of3-[1-methyl-3-(5-t-butyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 32 Preparation ofTetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone

The dimethyl acetal of3-[1-methyl-3-(5-t-butyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(16 grams), concentrated hydrochloric acid (10 ml) and water (500 ml)are charged into a glass reaction vessel equipped with a mechanicalstirrer, thermometer and reflux condenser. The reaction mixture isheated at reflux for a period of about 15 minutes. The reaction mixtureis filtered while hot and the filtrate is then cooled, resulting in theformation of a precipitate. The precipitate is recovered by filtration,dried and is recrystallized to yield the desired producttetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 33 Preparation ofTetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3,4-dichlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N-methyl-N-(3,4-dichlorophenyl)carbamoyl chloride (0.06mole), pyridine (0.06 mole) and toluene (150 ml) are charged into aglass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux withstirring for a period of about 3 horus. After this time the reactionmixture is cooled to room temperature and is filtered to remove pyridinehydrochloride. The filtrate is then washed with water, dried overanhydrous magnesium sulfate and stripped of solvent leaving a residue.The residue is recrystallized to yield the desired producttertrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3,4-dichlorophenyl)carbamoyloxy]-2(1H-pyrimidinone.

EXAMPLE 34 Preparation of the Diethyl Acetal of3-But-3-enylaminopropionaldehyde

But-3-enylamine (1.0 mole), the diethyl acetal of 3-bromopropionaldehyde(1.0 mole) and methanol (100 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux with stirring for aperiod of about 6 hours. After this time the reaction mixture is cooledto room temperature and sodium hydroxide (20 grams) is added. Thereaction mixture is then stirred for an additional period of about 16hours. The mixture is then filtered and the filtrate is distilled toyield the desired product the diethyl acetal of3-but-3-enylaminopropionaldehyde.

EXAMPLE 35 Preparation of the Diethyl Acetal of3-[1-But-3-enyl-3-(5-methoxy-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-methoxy-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05mole), the diethyl acetal of 3-but-3-enylaminopropionaldehyde (0.1 mole)and benzene (60 ml) are charged into a glass reaction vessel equippedwith a mechanical stirrer and reflux condenser. The reaction mixture isheated at reflux for a period of about 15 minutes. After this tine themixture is stripped of benzene under reduced pressure to yield thedesired product the diethyl acetal of3-[1-but-3-enyl-3-(5-methoxy-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 36 Preparation ofTetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-but-3-enyl-6-hydroxy-2(1H)-pyrimidinone

The diethyl acetal of3-[1-but-3-enyl-3-(5-methoxy-1,3,4-thiadizol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-but-3-enyl-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 37 Preparation ofTetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-but-3-enyl-6-(N-methyl-N-cyclohexylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-but-3-enyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N-methyl-N-cyclohexylcarbamoyl chloride (0.06 mole),pyridine (0.06 mole) and toluene (150 ml) are charged into a glassreaction vessel equipped with a mechanical stirrer, thermometer andreflux condenser. The reaction mixture is heated at reflux with stirringfor a period of about 3 hours. After this time the reaction mixture iscooled to room temperature and is filtered to remove pyridinehydrochloride. The filtrate is then washed with water, dried overanhydrous magnesium sulfate and stripped of solvent leaving a residue.The residue is recrystallized to yield the desired producttetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-but-3-enyl-6-(N-methyl-N-cyclohexylcarbamoyloxy)-2(1H)-pyrimidinone.

EXAMPLE 38 Preparation of the Diethyl Acetal of3-(1,1-Dimethylprop-2-ynylamino)propionaldehyde

1,1-Dimethylprop-2-ynylamine (1.0 mole), the diethyl acetal of3-bromopropionaldehyde (1.0 mole) and methanol (100 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux withstirring for a period of about 6 hours. After this time the reactionmixture is cooled to room temperature and sodium hydroxide (20 grams) isadded. The reaction mixture is then stirred for an additional period ofabout 16 hours. The mixture is then filtered and the filtrate isdistilled to yield the desired product the diethyl acetal of3-(1,1-dimethylprop-2-ynylamino)propionaldehyde.

EXAMPLE 39 Preparation of the Diethyl Acetal of3-[1-(1,1-Dimethylprop-2-ynyl)-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde

A mixture of 5-trifluoromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer(0.05 mole), the diethyl acetal of3-(1,1-dimethylprop-2-ynylamino)propionaldehyde (0.1 mole) and benzene(60 ml) are charged into a glass reaction vessel equipped with amechanical stirrer and reflux condenser. The reaction mixture is heatedat reflux for a period of about 15 minutes. After this time the mixtureis stripped of benzene under reduced pressure to yield a solid productas the residue. The residue is then recrystallized to yield the desiredproduct the diethyl acetal of3-[1-(1,1-dimethylprop-2-ynyl)-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde.

EXAMPLE 40 Preparation ofTetrahydro-1-(5-troifluoromethyl-1,3,4-thiadiazol-2-yl)-3-(1,1-dimethylprop-2-ynyl)-6-hydroxy-2(1H)-pyrimidinone

The diethyl acetal of3-[1-(1,1-dimethylprop-2-ynyl)-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde(15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged intoa glass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux for aperiod of about 15 minutes. The reaction mixture is then filtered whilehot and the filtrate is cooled to form a precipitate. The precipitate isrecovered by filtration, is dried and is recrystallized to yield thedesired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3(1,1-dimethylprop-2-ynyl)-6-hydroxy-2(1H)-pyrimidinone.

EXAMPLE 41 Preparation ofTetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-(1,1-dimethylprop-2-ynyl)-6-[N-ethyl-N-(2-methoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-(1,1-dimethylprop-2-ynyl)-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N-ethyl-N-(2-methoxyphenyl)carbamoyl chloride (0.06 mole),pyridine (0.06 mole) and toluene (150 ml) are charged into a glassreaction vessel equipped with a mechanical stirrer, thermometer andreflux condenser. The reaction mixture is heated at reflux with stirringfor a period of about 3 hours. After this time the reaction mixture iscooled to room temperature and is filtered to remove pyridinehydrochloride. The filtrate is then washed with water, dried overanhydrous magnesium sulfate and stripped of solvent leaving a residue.The residue is recrystallized to yield the desired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-(1,1-dimethylprop-2-ynyl)-6-[N-ethyl-N-(2-methoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 42 Preparation ofTetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-iodophenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and iodophenyl isocyanate (3.5 ml; 0.06 mole) are chargedinto a glass reaction vessel equipped with a mechanical stirrer. Themixture is stirred and triethylamine (1 drop) is added thereto. Afterthe addition is completed the reaction mixture is allowed to stand for aperiod of about 1 hour. The mixture is then washed with hexane and isdried to yield the desired producttetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-iodophenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 43 Preparation ofTetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2,4-dimethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole) and 2,4-dimethylphenyl isocyanate (3.5 ml; 0.06 mole) arecharged into a glass reaction vessel equipped with a mechanical stirrer.The mixture is stirred and triethylamine (1 drop) is added thereto.After the addition is completed the reaction mixture is allowed to standfor a period of about 1 hour. The mixture is then washed with hexane andis dried to yield the desired producttetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2,4-dimethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 44 Preparation ofTetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3-chloromethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone

Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N-methyl-N-(3-chloromethylphenyl)carbamoyl chloride (0.06mole), pyridine (0.06 mole) and toluene (150 ml) are charged into aglass reaction vessel equipped with a mechanical stirrer, thermometerand reflux condenser. The reaction mixture is heated at reflux withstirring for a period of about 3 hours. After this time the reactionmixture is cooled to room temperature and is filtered to remove pyridinehydrochloride. The filtrate is then washed with water, dried overanhydrous magnesium sulfate and stripped of solvent leaving a residue.The residue is recrysallized to yield the desired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3-chloromethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone.

EXAMPLE 45 Preparation ofTetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N-hexyl-N-methylcarbamoyloxy)-2(1H)-pyrimidinone

Tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone(0.05 mole), N-hexyl-N-methylcarbamoyl chloride (0.06 mole), pyridine(0.06 mole) and toluene (150 ml) are charged into a glass reactionvessel equipped with a mechanical stirrer, thermometer and refluxcondenser. The reaction mixture is heated at reflux with stirring for aperiod of about 3 hours. After this time the reaction mixture is cooledto room temperature and is filtered to remove pyridine hydrochloride.The filtrate is then washed with water, dried over anhydrous magnesiumsulfate and stripped of solvent leaving a residue. The residue isrecrystallized to yield the desired producttetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N-hexyl-N-methylcarbamoyloxy)-2(1H)-pyrimidinone.

Additional compounds of the present invention which may be prepared bythe procedures of the foregoing examples aretetrahydro-1-(5-allyl-1,3,4-thiadiazol-2-yl)-3-chloromethyl-6-[N-(2-methoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-butyl-6-(N-ethylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-isopropyl-1,3,4-thiadiazol-2-yl)-3-pentyl-6-(N-propylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-hexyl-1,3,4-thiadiazol-2-yl)-3-hexyl-6-(N-butylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-but-3-enyl-1,3,4-thiadiazol-2-yl)-3-hex-3-enyl-6-(N-pentylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-hex-4-enyl-1,3,4-thiadiazol-2-yl)-3-trifluoromethyl-6-(N-hexylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(-chloromethyl-1,3,4-thiadiazol-2-yl)-3-β-bromoethyl-6-(N,N-dimethylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-β-chloroethyl-1,3,4-thiadiazol-2-yl)-3-β,β,β-trichloroethyl-6-(N,N-diethylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-Γ-bromopropyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-(N,N-dihexylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-ethoxy-1,3,4-thiadiazol-2-yl)-3-(1,1-diethylprop-2-ynyl)-6-(N-cyclobutylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-propoxy-1,3,4-thiadiazol-2-yl)-3-(1,1-dipropylprop-2-ynyl)-6-(N-cyclopentylphenylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-butoxy-1,3,4-thiadiazol-2-yl)-3-(1,1-dibutylprop-2-ynyl)-6-(N-cycloheptylcarbamoyloxy)-2(1H)-pyrimidinone,tetrahydro-1-(5-hexyloxy-1,3,4-thiadiazol-2-yl)-3-(1,1-dihexylprop-2-ynyl)-6-[N-(2-ethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-ethylthio-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2-propylphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-propylthio-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-butylphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-pentylthio-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-hexylphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-ethylsulfonyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-fluorophenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-butylsulfonyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-trifluoromethylphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-hexylsulfonyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2-methoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-ethylsulfinyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2-ethoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-pentylsulfinyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(2,6-methoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-hexylsulfinyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(3-propoxyphenyl)carbamoyloxy]-2(1H)-pyrimidinone,tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-(4-hexyloxyphenyl)carbamoyloxy]-2(1H)-pyrimidinoneand the like.

For practical use as herbicides the compounds of this invention aregenerally incorporated into herbicidal compositions which comprise aninert carrier and a herbicidally toxic amount of such a compound. Suchherbicidal compositions, which can also be called formulations, enablethe active compound to be applied conveniently to the site of the weedinfestation in any desired quantity. These compositions can be solidssuch as dusts, granules, or wettable powders; or they can be liquidssuch as solutions, aerosols, or emulsifiable concentrates.

For example, dusts can be prepared by grinding and blending the activecompound with a solid inert carrier such as the talcs, clays, silicas,pyrophyllite, and the like. Granular formulations can be prepared byimpregnating the compound, usually dissolved in a suitable solvent, ontoand into granulated carriers such as the attapulgites or thevermiculties, usually of a particle size range of from about 0.3 to 1.5mm. Wettable powders, which can be dispersed in water or oil to anydesired concentration of the active compound, can be prepared byincorporating wetting agents into concentrated dust compositions.

In some cases the active compounds are sufficiently soluble in commonorganic solvents such as kerosene or xylene so that they can be useddirectly as solutions in these solvents. Frequently, solutions ofherbicides can be dispersed under super-atmospheric pressure asaerosols. However, preferred liquid herbicidal compositions areemulsifiable concentrates, which comprise an active compound accordingto this invention and as the inert carrier, a solvent and an emulsifier.Such emulsifiable concentrates can be extended with water and/or oil toany desired concentration of active compound for application as spraysto the site of the weed infestation. The emulsifiers most commonly usedin these concentrates are nonionic or mixtures of nonionic with anionicsurface-active agents. With the use of some emulsifier systems aninverted emulsion (water in oil) can be prepared for direct applicationto weed infestations.

A typical herbicidal composition according to this invention isillustrated by the following example, in which the quantities are inparts by weight.

EXAMPLE 46Preparation of aDust______________________________________Product of Example 510Powdered Talc 90______________________________________

The above ingredients are mixed in a mechanical grinder-blender and areground until a homogeneous, free-flowing dust of the desired particlesize is obtained.

This dust is suitable for direct application to the site of the weedinfestation.

The compounds of this invention can be applied as herbicides in anymanner recognized by the art. One method for the control of weedscomprises contacting the locus of said weeds with a herbicidalcomposition comprising an inert carrier and as an essential activeingredient, in a quantity which is herbicidally toxic to said weeds, acompound of the present invention. The concentration of the newcompounds of this invention in the herbicidal compositions will varygreatly with the type of formulation and the purpose for which it isdesigned, but generally the herbicidal compositions will comprise fromabout 0.05 to about 95 percent by weight of the active compounds of thisinvention. In a preferred embodiment of this invention, the herbicidalcompositions will comprise from about 5 to about 75 percent by weight ofthe active compound. The compositions can also comprise such additionalsubstances as other pesticides, such as insecticides, nematocides,fungicides, and the like; stabilizers, spreaders, deactivators,adhesives, stickers, fertilizers, activators, synergists, and the like.

The compounds of the present invention are also useful when combinedwith other herbicides and/or defoliants, dessicants, growth inhibitors,and the like in the herbicidal compositions heretofore described. Theseother materials can comprise from about 5% to about 95% of the activeingredients in the herbicidal compositions. Use of combinations of theseother herbicides and/or defoliants, dessicants, etc. with the compoundsof the present invention provide herbicidal compositions which are moreeffective in controlling weeds and often provide results unattainablewith separate compositions of the individual herbicides. The otherherbicides, defoliants, dessicants and plant growth inhibitors, withwhich the compounds of this invention can be used in the herbicidalcompositions to control weeds, can include chlorophenoxy herbicides suchas 2,4-D, 2,4,5-T MCPA, MCPB, 4(2,4-DB), 2,4-DEB, 4-CPB, 4-CPA, 4-CPP,2,4,5-TB, 2,4,5-TES, 3,4-DA, silvex and the like; carbamate herbicidessuch as IPC, CIPC, swep, barban, BCPC, CEPC, CPPC, and the like;thiocarbamate and dithiocarbamate herbicides such as CDEC, methamsodium, EPTC, diallate, PEBC, perbulate, vernolate and the like;substituted urea herbicides such as norea, siduron, dichloral urea,chloroxuron, cycluron, fenuron, monuron, monuron TCA, diuron, linuron,monolinuron, neburon, buturon, trimeturon and the like; symmetricaltriazine herbicides such as simazine, chlorazine, atraone, desmetryne,norazine, ipazine, prometryn, atazine, trietazine, simetone, prometone,propazine, ametryne and the like; chloroacetamide herbicides such as4-(chloroacetyl)morpholine, 1-(chloroacetyl)piperidine and the like;chlorinated aliphatic acid herbicides such as TCA, dalapon,2,3-dichloropropionic acid, 2,2,3-TPA and the like; chlorinated benzoicacid and phenylacetic acid herbicides such as 2,3,6-TBA, 2,3,5,6-TBA,dicamba, tricamba, amiben, fenac, PBA,2-methoxy-3,6-dichlorophenylacetic acid,3-methoxy-2,6-dichlorophenylacetic acid,2-methoxy-3,5,6-trichlorophenylacetic acid, 2,4-dichloro-3-nitrobenzoicacid and the like; and such compounds as aminotriazole, maleichydrazide, phenyl mercuric acetate, endothal, biuret, technicalchlordane, dimethyl 2,3,5,6-tetrachloroterephthalate, diquat, erbon,DNC, DNBP, dichlobenil, DPA, diphenamid, dipropalin, trifluralin, solan,dicryl, merphos, DMPA, DSMA, MSMA, potassium azide, acrolein, benefin,bensulide, AMS, bromacil,2-(3,4-dichlorophenyl)-4-methyl-1,2,4-oxadiazolidine-3,5-dione,bromoxynil, cacodylic acid, CMA, CPMF, cypromid, DCB, DCPA, dichlone,diphenatril, DMTT, DNAP, EBEP, EXC, HCA, ioxynil, IPX, isocil, potassiumcyanate, MAA, MAMA, MCPES, MCPP, MH, molinate, NPA, OCH, paraquat, PCP,picloram, DPA, PCA, pyrichlor, sesone, terbacil, terbutol, TCBA,brominil, CP-50144, H-176-1, H-732, M-2901, planavin, sodiumtetraborate, calcium cyanamid, DEF, ethyl xanthogen disulfide, sindone,sindone B, propanil and the like.

Such herbicides can also be used in the methods and compositions of thisinvention in the form of their salts, esters, amides, and otherderivatives whenever applicable to the particular parent compounds.

Weeds are undesirable plants growing where they are not wanted, havingno economic value, and interfering with the production of culivatedcrops, with the growing of ornamental plants, or with the welfare oflivestock. Many types of weeds are known, including annuals such aspigweed, lambsquarters, foxtail, crabgrass, wild mustard, fieldpennycress, ryegrass, goose grass, chickweed, wild oats, velvetleaf,purslane, barnyardgrass, smartweed, knotweed, cocklebur, wild buckwheat,kochia, medic, corn cockle, ragweed, sowthistle, coffeeweed, croton,cuphea, dodder, fumitory, groundsel, hemp nettle, knawel, spurge,spurry, emex, jungle rice, pondweed, dog fennel, carpetweed,morningglory, bedstraw, ducksalad, naiad, cheatgrass, fall panicum,jimsonweed, witchgrass, switchgrass, watergrass, teaweed, wild turnipand sprangletop; biennials such as wild carrot, matricaria, wild barley,campion, chamomile, burdock, mullein, roundleaved mallow, bull thistle,hounds-tongue, moth mullein and purple star thistle; or perennials suchas white cockle, perennial ryegrass, quackgrass, Johnson grass, Canadathistle, hedge bindweed, Bermuda grass, sheep sorrel, curly dock,nutgrass, field chickweed, dandelion, campanula, field bindweed, Russianknatweed, mesquite, toadflax, yarrow, aster, gromwell, horsetail,ironweed, sesbania, bulrush, cattail, wintercress, horsenettle,nutsedge, milkweed and sicklepod.

Similarly, such weeds can be classified as broadleaf or grassy weeds. Itis economically desirable to control the growth of such weeds withoutdamaging beneficial plants or livestock.

The new compounds of this invention are particularly valuable for weedcontrol because they are toxic to many species and groups of weeds whilethey are relatively non-toxic to many beneficial plants. The exactamount of compound required will depend on a variety of factors,including the hardiness of the particular weed species, weather, type ofsoil, method of application, the kind of beneficial plants in the samearea, and the like. Thus, while the application of up to only about oneor two ounces of active compound per acre may be sufficient for goodcontrol of a light infestation of weeds growing under adverseconditions, the application of ten pounds or more of an active compoundper acre may be required for good control of a dense infestation ofhardy perennial weeds growing under favorable conditions.

The herbicidal toxicity of the new compounds of this invention can bedemonstrated by the following established testing techniques known tothe art, pre- and post-emergence testing.

The herbicidal activity of the compounds of this invention can bedemonstrated by experiments carried out for the pre-emergence control ofa variety of weeds. In these experiments small plastic greenhouse potsfilled with dry soil are seeded with the various weed seeds. Twenty-fourhours or less after seeding the pots are sprayed with water until thesoil is wet and a test compound formulated as an aqueous emulsion of anacetone solution containing emulsifiers is sprayed at the desiredconcentrations on the surface of the soil.

After spraying, the soil containers are placed in the greenhouse andprovided with supplementary heat as required and daily or more frequentwatering. The plants are maintained under these conditions for a periodof from 15 to 21 days, at which time the condition of the plants and thedegree of injury to the plants is rated on a scale of from 0 to 10, asfollows: 0 = no injury, 1,2 = slight injury, 3,4 = moderate injury, 5,6= moderately severe injury, 7,8,9 = severe injury and 10 = death.

The herbicidal activity of the compounds of this invention can also bedemonstrated by experiments carried out for the post-emergence controlof a variety of weeds. In these experiments the compounds to be testedare formulated as aqueous emulsions and sprayed at the desired dosage onthe foliage of the weeds that have attained a prescribed size. Afterspraying the plants are placed in a greenhouse and watered daily or morefrequently. Water is not applied to the foliage of the treated plants.The severity of the injury is determined 10 to 15 days after treatmentand is rated on the scale of from 0 to 10 heretofore described.

I claim:
 1. A compound of the formula ##EQU13## wherein R¹ is selectedfrom the group consisting of lower alkyl, lower alkenyl, lowerchloroalkyl, lower bromoalkyl, trifluoromethyl, lower alkoxy, loweralkylthio, lower alkylsulfonyl and lower alkylsulfinyl; R² is selectedfrom the group consisting of lower alkyl, lower alkenyl, lowerchloroalkyl, lower bromoalkyl and ##EQU14## wherein R³ and R⁴ are eachselected from the group consisting of hydrogen and lower alkyl; R⁵ isselected from the group consisting of hydrogen and lower alkyl; and R⁶is selected from the group consisting of lower alkyl, cycloalkyl of from3 to 7 carbon atoms and ##SPC4##wherein X is selected from the groupconsisting of lower alkyl, halogen, lower haloalkyl and lower alkoxy,and n is an integer from 0 to
 3. 2. The compound of claim 1, which istetrahydro-1-(5-methyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N-methylcarbamoyloxy)-2(1H)-pyrimidinone.3. The compound of claim 1, which istetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-(N-cyclopropylcarbamoyloxy)-2(1H)-pyrimidinone.4. The compound of claim 1, which istetrahydro-1-(5-methylthio-1,3,4-thiadiazol-2-yl)-3-propyl-6-(N-cyclohexylcarbamoyloxy)-2(1H)-pyrimidinone.5. The compound of claim 1, which istetrahydro-1-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)-3-allyl-6-[N-(3-chlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone.6. The compound of claim 1, which istetrahydro-1-(5-methylsulfinyl-1,3,4-thiadiazol-2-yl)-3-propargyl-6-[N-(2-methyl-4-bromophenyl)carbamoyloxy]-2(1H)-pyrimidinone.7. The compound of claim 1, which istetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-(N,N-dimethylcarbamoyloxy)-2(1H)-pyrimidinone.8. The compound of claim 1, which istetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3,4-dichlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone.